Henderson P J
Biochem J. 1972 Apr;127(2):321-33. doi: 10.1042/bj1270321.
When an enzyme exhibits a high affinity for an inhibitor, the steady-state analysis of the mechanism is complicated by the non-linearity of normal dose-response plots or of reciprocal replots. It is shown here that dose-response measurements generate a linear plot of inhibitor concentration divided by degree of inhibition against velocity without inhibitor divided by velocity with inhibitor; the concentration of enzyme may be derived from the extrapolated intercept of such plots, and the mechanism of inhibition from replots of the variation of the slope with substrate concentration. The limiting cases where virtually all inhibitor molecules are bound or virtually all are free are described, together with the situation when a significant proportion of the substrate becomes bound. This type of analysis indicates that the inhibitors of oxidative phosphorylation, rutamycin and bongkrekic acid, are tightly bound to rat liver mitochondria.
当一种酶对抑制剂表现出高亲和力时，正常剂量-反应曲线或双倒数重绘图的非线性会使该机制的稳态分析变得复杂。本文表明，剂量-反应测量产生了一个线性图，即抑制剂浓度除以抑制程度与无抑制剂时的速度除以有抑制剂时的速度之比；酶的浓度可以从此类图的外推截距得出，而抑制机制可从斜率随底物浓度变化的重绘图中得出。文中描述了几乎所有抑制剂分子都结合或几乎所有都游离的极限情况，以及相当比例的底物发生结合的情况。这种分析类型表明，氧化磷酸化抑制剂如路他霉素和邦克酸与大鼠肝脏线粒体紧密结合。
